Interpretive Summary: In this study, the ferret model was used to demonstrate that vaccination with the seasonal (2010-11) trivalent inactivated influenza vaccine (TIV) induced neutralizing antibodies to the H1N1 1918 virus, which was the cause one of the worst pandemics in human history. Vaccinated ferrets demonstrated a significant reduction in viral shedding and body temperatures following 1918 virus challenge. Vaccination with TIV also prevented significant virus replication in the lung and trachea of ferrets on subsequent challenge, further demonstrating that the current influenza vaccine would provide protection against the 1918 pandemic virus. The results of this study help in understanding the mechanisms of influenza virus transmission and have implications for biosafety and biosecurity precautions that are designed to protect workers and the public from possible exposure to this virus.

Technical Abstract:
The influenza H1N1 pandemic of 1918 was one of the worst medical disasters in human history. Recent studies have demonstrated that the hemagglutinin (HA) protein of the 1918 virus and 2009 H1N1 pandemic virus, the latter now a component of the seasonal trivalent inactivated influenza vaccine (TIV), share cross-reacting antigenic determinants. In this study, we demonstrate that previous exposure to the 2010-11 seasonal TIV is able to induce 1918 virus-specific neutralizing antibodies in ferrets. TIV-immunized ferrets subsequently challenged with the 1918 pandemic virus displayed a significant reduction in body temperature, weight loss and virus shedding compared to non-immune control ferrets. In a second vaccine-challenge experiment, seasonal TIV was also effective in protecting against lung infection and severe lung pathology associated with 1918 virus infection. Our data demonstrate that prior immunization with contemporary TIV provides cross-protection against the 1918 virus, further alleviating concerns regarding its potential use as a bioterrorism agent and the accidental exposure or release of this pandemic strain from the laboratory.